A variety of medical techniques suitable for imaging biological tissues and organs are known. These include traditional x-rays, ultra-sound, magnetic resonance imaging, and computerized tomography.
A variety of dyes useful for medical imaging have been described, including radio opaque dyes, fluorescent dyes, and calorimetric dyes (see e.g., U.S. Pat. Nos. 5,699,798; 5,279,298; 6,351,663). Imaging techniques and systems using fluorescent dyes have been described for the heart and eye (see, e.g., U.S. Pat. No. 5,279,298). Some dyes can serve both an imaging function and a therapeutic function (see, e.g. U. S. Pat. No. 6,840,933). Some specific neuronal imaging agents have been used to visualize tissue in the central nervous system. Tracer uptake and transport has been demonstrated in different studies using various routes of administration including antegrade, retrograde and combined routes (Jones et al. 1978, Annu Rev Neurosci.; 1:215; Rosina A., 1982, Neurosci Lett. 33(3):217; Illing RB, et al., 1985, Neuroscience 14(2):455; Sloniewski P, et al., 1985, Neurosci Lett. 60(2):189; and Schmued et al., 1986, Brain Res. 377(1):147). After appropriate time for endo/pinocytosis, perineural lymphatic and axonal transport, which generally measures 0.5-2 mm per hour, tracers were visually detected using ultraviolet or visible light (Bentivoglio et al., 1980, Neurosci Lett. 18(1):19; Minciacchi D et al., 1991, J Neurosci Methods. 38(2-3):183). Non-toxic tracers such as Indocyanine Green, Fast Blue, and Fluorogold, have been used in mammals without evidence of neuronal toxicity several months after the treatment (Thielert et al., 1993, J Comp Neurol. 337(1):113; Yeterian et al., 1994, Exp Brain Res. 99(3):383; vogt Weisenhorn et al., 1995, J Comp Neurol. 362(2):233). Marangos et al. labeled the auditory nerve using Fluorogold and Fast Blue in rats and monkeys by suctioning out perilymph and filling the cochlea with neuronal tracers to identify the nerve and cochlear brain stem nucleus for the positioning of electrodes for an auditory neuroprosthesis (Marangos N, et al., 2001, Hear Res. 162(1-2):48).
The prostate is an accessory sex gland in men. It is about the size of a walnut, and surrounds the neck of the bladder and the urethra, the tube that carries urine from the bladder. It is partly muscular and partly glandular, with ducts opening into the prostatic portion of the urethra. It is made up of three lobes: a center lobe with one lobe on each side. The prostate gland secretes a slightly alkaline fluid that forms part of the seminal fluid.
Prostate cancer is the most common type of cancer (excluding skin cancer) among American men. It is found most often in men aged 50 and over, with an especially high prevalence rate among African Americans. In men, it is second only to lung cancer as a cause of cancer-related death. The American Cancer Society has estimated that 220,900 new cases of prostate cancer will be diagnosed annually and that 28,900 men annually will die of the disease (Cancer Facts and Figures, American Cancer Society, 2003). Treatment options include hormonal therapy aimed at lowering testosterone levels, radiation therapy, chemo therapy and surgery.
Surgical removal of the entire prostate gland is called radical prostatectomy (“RP”). The aim of radical prostatectomy is removal of early-stage prostate cancer, one that has not yet spread locally or to distant organs. Radical prostatectomy complications include incontinence and impotence. Most men experience urinary incontinence after surgery. Many continue to have intermittent problems with dribbling caused by coughing or exertion. Damage to nerves which innervate both the prostate and the penis plays a significant part in these unwanted side effects. Approximately 40 to 60% of men undergoing RP are impotent due to injury to the cavernous nerves during the surgery.
Topographically, cavernous nerves are part of the neurovascular bundle, which travels at the posterolateral border of the prostate, outside the prostatic capsule and on the anterolateral surface of the rectum. McNeal described large superior and small inferior pedicles innervating the base and the apex of the prostate respectively (McNeal J E., 1988, Am J Surg Pathol.; 12(8):619.). After reaching the apex at the 5 and 7-o'clock positions, nerves travel posterolaterally to the urethra. At the level of membranous urethra they divide into more superficial branches to the sphincter muscle and finally at the level of the hilum of the penis, together with the arteries, the nerves pierce the cavernous bodies and innervate erectile tissue diffusely (Lue et al., 1983, J Urol.; 130(6):1237; Breza et al., 1989, J Urol. 141(2):437).
The risk of impotence may be reduced by avoiding cutting or stretching bundles of nerves and blood vessels that run along the surface of the prostate gland and are needed for an erection. Successful nerve sparing surgery, however, is often difficult to achieve because of the difficulty in distinguishing between the prostate tissue, in particular the cancerous prostate tissue, and the innervating nerve tissue. Appropriate mapping of the nerves can also lead to better understanding of cavernous nerves topography and penile accessory innervation. Accordingly, a need exists for improved methods of imaging peripheral nerves, such as the nerves which innervate the prostate. The present invention fills these and other needs.